The problem addressed by the present invention is how to nonsurgically implant a solid, often load-bearing, mass of biomaterial. The simple solution is to formulate the mass as an aqueous suspension of particles and inject it with a syringe or similar instrument into the tissue at the desired site. Depending on the material used and its concentration in the suspension, the injectability of the suspension may be less than adequate. Such inadequacy may manifest itself in terms of difficulties in extruding the suspension through a fine gauge needle and/or poor intrusion into the tissue. Common extrusion difficulties are excessive or irregular extrusion pressures and needle blockage. Poor intrusion is characterized by a tendency for the implant to intrude the tissue as a uniform front and form a solid bead rather than fingering into the tissue and forming a relatively dispersed, irregular-shaped mass.
Several prior U.S. patents or applications that are owned or licensed to the assignee of the present invention relate to injectable collagen-based implants for soft tissue augmentation.
U.S. Pat. No. 3,949,073 describes the use of a solution of atelopeptide collagen as an injectable implant for augmenting soft tissue. The solution is brought to physiological ionic strength and pH and injected with a small gauge needle. The collagen fibers reconstitute to produce a fibrous mass of collagen at the injection site. Since the solid content of the injected material is low and the reconstituted fibers are flexible and small, there are no extrusion or intrusion problems with this material.
U.S. Pat. No. 4,424,208 concerns an implant material comprised of a mixture of solid elastic particles of cross-linked collagen and reconstituted collagen fibers. While this material was injectable through medium gauge needles, its extrusion and intrusion properties were poor. The material did, however, exhibit improved persistence over the reconstituted uncross-linked material of U.S. Pat. No. 3,949,073 described above.
A cross-linked collagen implant material having improved extrusion properties over that described in U.S. Pat. No. 4,424,208 is claimed in commonly owned U.S. Pat. No. 4,582,640. This material was prepared under cross-linking conditions that produced predominantly intrafibrillar cross-links. In addition to lower viscosity, this "lightly cross-linked" collagen exhibits better persistence and resistance to proteolytic digestion than the previous materials. The extrudability of this material was improved further by mechanically shearing the reconstituted fibers before cross-linking. This mechanicaly shared, cross-linked collagen is the subject of commonly owned U.S. patent application Ser. No. 715,098, filed Mar. 22, 1985. Clinical testing of this improved material indicated that its intrudability was less than desired, particularly when it was injected intradermally for cosmetic purposes.
The present invention provides the technology for improving the injectability of implant suspensions of particulate biomaterials, such as the cross-linked collagen of the above-mentioned U.S. Patent Application, even further.